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Label indication DALIRESP ® is indicated as a treatment to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. DALIRESP is a selective phosphodiesterase 4 inhibitor indicated as a treatment to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. FDA label
Also known as DALIRESP®, DAXAS®
Roflumilast · 1 trial · 1 indication
The Spatial Span test assesses the participant's working memory. During this task, participants are presented with a board containing blue blocks randomly arranged. The rater first taps out a pattern of blocks, beginning with two blocks and increasing with participant proficiency, and the participant is tasked with tapping the same pattern. After discontinuation of this part of the subtest, the participant is then tasked with tapping out the reverse pattern after the rater's demonstration. These patterns also begin with two blocks and increase with participant proficiency. The total score for this subtest ranges from 0 (worst) to 32 (best). A positive change from Baseline indicates improvement. Analysis of Variance (ANOVA) with treatment sequence, study period, and treatment as fixed effects and participant nested within treatment sequence as a random effect was used for analysis.
The HVLT assesses the participant's verbal learning. The test consists of a list of 12 words from three taxonomic categories which are presented orally, and the participant is asked to recall as many as possible after each of three learning trials. The key outcome variable for this task is the total correct responses in the three learning trials. A positive change from Baseline indicates improvement. ANOVA with treatment sequence, study period, and treatment as fixed effects and participant nested within treatment sequence as a random effect was used for analysis.
BOLD Functional magnetic resonance imaging (fMRI) changes in the blood-oxygen-level-dependent (BOLD) - signal, which changes in response to neural activity. Baseline fMRI measurements will be followed by rewarded delayed response Working Memory (WM) task measurements in which participants are required to remember the spatial location of a target stimulus (a dot) relative to a fixation cross. Participants are given feedback indicating success or failure. ANOVA with treatment sequence, study period, and treatment as fixed effects and participant nested within treatment sequence as a random effect.
| Arm | Type | Description |
|---|---|---|
| Placebo + Roflumilast 100 μg + Roflumilast 250 μg | EXPERIMENTAL | Roflumilast placebo-matching tablets, orally, once, daily, Days 1 through 8, Period 1, followed by a 14 day washout period, followed by roflumilast 100 μg tablets, orally, once, daily, Days 1 through 8, Period 2, followed by a 14 day washout period, followed by roflumilast 250 μg tablets, orally, once, daily, Days 1 through 8, Period 3. All participants will take a stable dose of second generation antipsychotics throughout the duration of the treatment period. |
| Roflumilast 100 μg + Roflumilast 250 μg + Placebo | EXPERIMENTAL | Roflumilast 100 μg tablets, orally, once, daily, Days 1 through 8, Period 1, followed by a 14 day washout period, followed by roflumilast 250 μg tablets, orally, once, daily, Days 1 through 8, Period 2, followed by a 14 day washout period, followed by roflumilast placebo-matching tablets, orally, once, daily, Days 1 through 8, Period 3. All participants will take a stable dose of second generation antipsychotics throughout the duration of the treatment period. |
| Roflumilast 250 μg + Placebo + Roflumilast 100 μg | EXPERIMENTAL | Roflumilast 250 μg tablets, orally, once, daily, Days 1 through 8, Period 1, followed by a 14 day washout period, followed by roflumilast placebo-matching tablets, orally, once, daily, Days 1 through 8, Period 2, followed by a 14 day washout period, followed by roflumilast 100 μg tablets, orally, once, daily, Days 1 through 8, Period 3. All participants will take a stable dose of second generation antipsychotics throughout the duration of the treatment period. |
| Name | Type | Description |
|---|---|---|
| Roflumilast | DRUG | Roflumilast tablets |
| Placebo | DRUG | Roflumilast placebo-matching tablets |
| Second generation antipsychotic | DRUG | Second Generation Antipsychotic (SGA) medication for standard of care therapy will be sourced and managed locally by the site. |
Inclusion Criteria: 1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. 2. Signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. 3. Meets schiz...
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Roflumilast is being studied as an add-on treatment for schizophrenia, where it is given alongside standard antipsychotic medication. It is a small molecule PDE4 inhibitor. The research is at an early stage: a single Phase 1 proof of mechanism trial has been completed, and the drug is not approved for schizophrenia.
Roflumilast inhibits phosphodiesterase 4, specifically the PDE4A, PDE4D, PDE4B, and PDE4C subtypes. By blocking these enzymes, it raises intracellular cyclic AMP signaling. This PDE4 inhibitor mechanism is the basis for testing Roflumilast as an adjunct to antipsychotics in schizophrenia, a setting where cognitive and negative symptoms are often inadequately treated.
Takeda Pharmaceutical Company Limited, which trades under the ticker TAK, is the developer of Roflumilast for schizophrenia. The company sponsored the Phase 1 proof of mechanism study that evaluated the drug as an add-on to antipsychotic therapy in patients with schizophrenia.
Roflumilast is in Phase 1 development for schizophrenia. One Phase 1 trial has been completed, and no active trials are ongoing. It is an investigational use: Roflumilast has not been approved for schizophrenia, and the completed study was an early proof of mechanism trial rather than a registrational efficacy study.
The relevant study is NCT02079844, titled Roflumilast Plus Antipsychotics Proof of Mechanism Study in Schizophrenia. It was a Phase 1, randomized, double-blind, controlled trial that enrolled 20 participants aged 18 years and older in the United Kingdom. The trial is completed, and it did not select patients by biomarker.